Abiraterone - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Mineralocorticoid excess: Closely monitor patients with cardiovascular disease.

Control hypertension and correct hypokalemia before treatment.

Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency.

Increased dosage of corticosteroids may be indicated before, during and after stressful situations.

Hepatotoxicity: Can be severe and fatal.

Monitor liver function and modify, interrupt, or discontinue abiraterone acetate dosing as recommended.

Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride is not recommended.

Embryo-Fetal Toxicity: Abiraterone acetate can cause fetal harm.

Advise males with female partners of reproductive potential to use effective contraception. ( 5.5 , 8.1 , 8.3 ) Hypoglycemia: Severe hypoglycemia has been reported in patients with pre-existing diabetes who are taking medications containing thiazolidinediones (including pioglitazone) or repaglinide.

Monitor blood glucose in patients with diabetes and assess if antidiabetic agent dose modifications are required.

5.1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess Abiraterone acetate may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology ].

Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month.

Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate.

In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1,000 mg abiraterone acetate daily, grades 3 to 4 hypokalemia were detected in 4% of patients on the abiraterone acetate arm and 2% of patients on the placebo arm.

Grades 3 to 4 hypertension were observed in 2% of patients each arm and grades 3 to 4 fluid retention in 1% of patients each arm.

In LATITUDE (a randomized placebo-controlled, multicenter clinical trial), which used prednisone 5 mg daily in combination with 1,000 mg abiraterone acetate daily, grades 3 to 4 hypokalemia were detected in 10% of patients on the abiraterone acetate arm and 1% of patients on the placebo arm, grades 3 to 4 hypertension were observed in 20% of patients on the abiraterone acetate arm and 10% of patients on the placebo arm.

Grades 3 to 4 fluid retention occurred in 1% of patients each arm [see Adverse Reactions ].

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia.

In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate.

The safety of abiraterone acetate in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301 and LATITUDE) or NYHA Class II to IV heart failure (in COU-AA-302 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials [see Clinical Studies ].

5.2 Adrenocortical Insufficiency Adrenal insufficiency occurred in 0.3% of 2,230 patients taking abiraterone acetate and in 0.1% of 1,763 patients taking placebo in the combined data of the 5 randomized, placebo-controlled clinical studies.

Adrenocortical insufficiency was reported in patients receiving abiraterone acetate in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress.

Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress.

Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate.